With Ponatinib on the track for treatment-free-remission in chronic myeloid leukemia

Trial details

Who runs it

Heidelberg University

Trial code

EU 2024-518971-76-00

Record updated

2024. november 22.

Original description

Assessment of patients who achieved MR4 after 2 years of treatment with ponatinib.Read full original descriptionShow less

Assessment of patients who achieved MR4 after 2 years of treatment with ponatinib.

Inclusion: Female or male ≥ 18 years of age; Patients with CML in chronic phase (CP); BCR-ABL IS between 0,5-0,01 and demonstrated by the last PCR before inclusion; not achieving MR4 (defined as < 0,01% BCR-ABLIS) or not achieving a stable MR4 (defined as no continuous in MR4 during the last 12 months before inclusion) after ≥ 3 years of treatment with nilotinib, dasatinib and / or bosutinib in first or second line; Philadelphia -chromosome and/or BCR-ABL (either b3a2 and /or b2a2) fusion gene positive CML; Patients must have had an eye examination including fundoscopy by an ophthalmologist within 8 weeks prior to first treatment.

Exclusion: Prior diagnosis of accelerated phase (AP) or blast phase (BP) at any time in the history of the disease; Not able to take oral therapy; Previously planned or performed allogenic SCT; Venous thromboembolism, including deep venous thrombosis or pulmonary embolism, within 6 months prior to enrolment; Failure of any TKI at any time during CML treatment according to current ELN criteria (including any detection of mutations or additional cytogenetic aberrations); Positive hepatitis B virus serology test; Other severe or uncontrolled medical conditions(e.g. Infection); History of myocardial infarction; History of significant (as determined by the treating physician) atrial or ventricular arrhythmias; History of coronary heart disease; History of other clinically significant heart disease (e.g. unstable angina, congestive heart failure) or impaired cardiac function; History of hyperlipidaemia; History of cerebrovascular accident (CVA, e.g. stroke) or transient ischemic attack (TIA); History of peripheral vascular infarction, including visceral infarction or other vascular occlusive events; History of any revascularization procedure, (e.g. placement of stents, bypasses); History of moderate or severe acute or chronic liver disease; History of alcohol abuse; History of severe hypertriglyceridemia; High cardiac risk according to ESC score (≥ 10%) (results of screening); Moderate , severe or end-stage chronic renal disease unrelated to tumor; Bleeding issues; Any other malignancy except if neither clinically significant nor requires active intervention; Uncontrolled hypertension (diastolic blood pressure ≥ 90 mm Hg; systolic ≥ 140 mm Hg). Patients with hypertension should be under treatment on study entry to effect blood pressure control; No adequate hepatic function (total serum bilirubin > 1.5 × ULN, unless due to Gilbert’s syndrome; Alanine aminotransferase (ALAT) > 2.5 × ULN, or > 5 × ULN if leukemic infiltration of the liver is present; aspartate aminotransferase (ASAT) > 2.5 × ULN, or > 5 × ULN if leukemic infiltration of the liver is present); No adequate pancreatic function (serum lipase and amylase >1.5 × ULN); No adequate renal function [estimated creatinine clearance (eGFR) of < 90 ml/min; positive serum pregnancy test (of woman with childbearing potential); No willingness or ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures; History of congenital long QT syndrome or family; Severe diabetes with end organ damage (e.g. microalbuminuria) or poorly controlled diabetes, defined as HbA1c values over the previous year of > 7.5% (59 mmol/mol) on more than 3 occasions. Patients with pre-existing, well-controlled diabetes are not excluded; Treatment with inhibitors of CYP3A4 or medications that have been well documented to prolong the QT interval; Women who are pregnant or breast feeding; woman of childbearing potential not agreeing to use an higly-effective form of contraception or fertile male not agreeing to use an acceptable birth control method (for definition see appendix) with sexual partners throughout study participation until 90 days after EoT; Legally incapacitated; No ability to comprehend and sign the informed consent; Held in an institution by legal or official order; Participation in other clinical trials; Use of a ventricular paced pacemaker; Historiy of retinal venous occlusions; Either acute pancreatitis within 1 year before study entry or chronic pancreatitis; Renal artery stenosis; Clinically significant resting bradycardia (<50 bpm) or tachycardia (>100 bpm) (results of screening); QTcF interval on baseline electrocardiogram (ECG) evaluation, defined as QTcF of >450 ms in males or > 470 ms in females (results of screening); Ankle-brachial-index (ABI) < 0,9 or >1,4 or alternatively signs of arterial occlusion in duplex sonography.

EU CTIS 2024-518971-76-00